Plasma ceruloplasmin

It has been reported that ceruloplasmin increases iron uptake into cultured human cells (Mukhopadhyay et al, 1998), although this apparently contradictory in vitro observation must be set against the in vivo evidence presented above from both animal and human studies. Plasma ceruloplasmin levels increase markedly in anaemia, consistent with a physiological role in tissue iron mobilization, and this effect is due to transcriptional activation of ceruloplasmin mRNA synthesis (Mukhopadhyay et al, 2000). 

Contrary to popular belief, ceruloplasmin5, the principal copper-containing protein in plasma, ceruloplasmin, is not involved in copper transport. This is clearly underlined by the clinical observation that patients with aceruloplasminaemia (i.e. lacking ceruloplasmin in their blood) have perfectly normal copper metabolism and homeostasis. Copper is transported in plasma mostly by serum albumin with smaller amounts bound to low-molecular weight ligands like histidine. Likewise zinc is mostly transported in plasma bound to proteins (albumin and ot2-macroglobulin). 

Compound 34 is a triantennary, sialo glycopeptide terminated with NeuAc a-(2- 6)-linked to Gal in all three branches it could be obtained by exhaustive, in vitro sialylation of compound 9 with /3-D-ga-lactoside a-(2— 6)-sialyltransferase.13,78 The Gln-Asn analog of compound 34, in admixture with compound 53 and a glycopeptide analog of 41, has been isolated from human-plasma ceruloplasmin (see compound 53). The 500-MHz, -n.m.r. spectrum of 34 is given in Fig. 26, and its pertinent spectral parameters are listed in Table X. 

Defects in the copper-transporting ATPase 7B (ATP7B) causes Wilson s disease. The ATP7B transporter eliminates copper through the bile and also transports copper into plasma ceruloplasmin (see Metal-related Diseases of Genetic Origin) ... 

Experimentally induced copper deficiency produces anemia in a variety of animals. It produces an anemia. As one might expect, this type of anemia cannot be cured by iron. The heart may enlarge and the mitochondria of the heart may enlarge dramatically. The heart and arteries may rupture with deficiency, probably because of a drop in the activity of lysyl oxidase, a copper melallt enzyme involved in the synthesis of connective tissue proteins. Skeletal defects, such as osteoporosis, occur in experimental copper deficiency. Infections appear to affect copper metabolism. Infections can induce a threefold increase in plasma ceruloplasmin levels. Copper-deficient animals have a reduced ability to exercise, as measured by running on treadmills (Klevay and Medeiros, 1996). 

There is a variety of analytical methods used for ceruloplasmin determinations the most frequently used is the p-phenylenediamine oxidase method, by virtue of its high precision. The oxidation rate of p-phenylenediamine or a derivative is measured spectrophotometrically or gasometrically, determining ceruloplasmin oxidase activity. Sunderman and Nomoto (132) determined plasma ceruloplasmin by measuring... 

Sht lamp eye examination may detect copper deposits in the eye (Kayser-Fleischer rings) and there may be abnormalities in liver frinction tests with an increased urine copper output (>500 fig Cu per L). Liver biopsy for copper analysis is useful in suspected cases and results above 250 fXg/g Cu dry weight are usually found (normal 8 to 40 Xg Cu per g dry weight). Failure of copper incorporation into plasma ceruloplasmin can also be demonstrated using an oral dose of stable Cu isotope. This may be helpful in excluding Wilson s disease when other tests are equivocal. Gene tracking and mutation detection are now possible, but since several hundred mutations exist this may not be informative. 

Menkes syndrome (Menkes steely-hair syndrome) is a rare, X-linked recessive disorder in which infants have low levels of copper in serum and in most tissues except kidney and intestine, where the concentration is very high. They also have greatly reduced plasma ceruloplasmin levels. Hair of the affected infants has a characteristic color and texture (pili torti, twisted hair ). It appears tangled and dull, has an ivory or grayish color, and is friable. Weakness and depigmentation of hair and defects in arterial walls (leading to aneurysms) are explained by loss of activity of copper-dependent enzymes (Table 37-5). Cerebral dysfunction may be due to a disturbance in energy metabolism or neurotransmitter synthesis secondary to decreased activity of cytochrome oxidase and dopamine... 

Table V. Effects of Silver and Selenium on Plasma Ceruloplasmin Activity and on Plasma Silver, Copper, and Zinc Levels...

As shown in Table V, silver significantly depressed plasma copper levels and ceruloplasmin activity but had no influence on plasma zinc levels. As expected, silver accumulated in the plasma. The depressing effect of silver on ceruloplasmin activity is in agreement with earlier work (Whanger and Weswig, 1970). These workers found silver to have the most depressing effect on plasma ceruloplasmin activity, followed by cadmium, molybdenum, zinc, and sulfate in descending order. 

Plasma ceruloplasmin levels are normal. Ceruloplasmin is a copper-binding protein tiiat is prc uced in the liver and released to the plasma to bind copper. 

The mutant gene in individuals with Wilson s disease produces a yet-undiscovered biochemical defect that results in excess retention of hepatic copper. Most affected patients have a decreased concentration of plasma ceruloplasmin and excretion of copper into the bile is impaired. Thus, the defect apparently involves the mechanisms that regulate the passage of copper into the ceruloplasmin-synthesizing and biliary-excretion pathways. 

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